Phosphate metabolism in erythrocytes of critically ill patients

1985 ◽  
Vol 69 (4) ◽  
pp. 435-440 ◽  
Author(s):  
A. Bevington ◽  
A. J. Asbury ◽  
C. J. Preston ◽  
R. G. G. Russell
Keyword(s):  
Intensive Care Unit ◽  
Cell Function ◽  
Lactate Production ◽  
Atp Depletion ◽  
Mass Action ◽  
Phosphate Metabolism ◽  
Erythrocyte Concentration ◽  
Hydrolysis Of ◽  
2,3 Dpg ◽  
Stimulation Of

1. Orthophosphate (Pi), adenosine 5′-diphosphate (ADP), adenosine 5′-triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) were measured in the erythrocytes of patients in an intensive care unit. 2. The patients’ plasma concentration of Pi varied from 0.1 to 4.2 mmol/l, and the corresponding concentration in erythrocytes varied from 0.1 to 2.0 mmol/litre of cells. 3. Marked ATP depletion (less than 1 mmol/litre of cells) was only observed when erythrocyte Pi was less than 0.3 mmol/litre of cells and plasma Pi was less than 0.35 mmol/l. No dependence of 2,3-DPG concentration on the cellular concentration of Pi was detected. 4. The phosphorylation potential [ATP]/([ADP] × [Pi]) varied inversely with the erythrocyte concentration of Pi. Hence the calculated free energy of hydrolysis of ATP in the cell increased from −58 kJ/mol in the most hypophosphataemic samples to −51 kJ/mol in the most hyperphosphataemic. Such changes may adversely affect cell function by altering the steady state mass-action ratios of ATPase reactions. 5. When erythrocytes from normal donors were incubated in solutions containing 1 or 5 mmol/l Pi, the cellular concentrations of Pi stabilized at 1.09 and 2.85 mmol/litre of cells respectively. The corresponding rates of lactate production were 2.09 and 3.11 mmol h−1 litre−1 of cells. 6. In spite of this stimulation of glycolysis (and hence of the flux through ATP synthesizing steps of the Embden-Meyerhof pathway), no significant change in ATP concentration was observed. As in the patients' cells, this indicates that, when extracellular Pi concentrations are perturbed, the concentrations, in erythrocytes, of organic phosphates are more closely regulated than the concentration of Pi.

scholarly journals Regulation of rat Sertoli cell function by FSH: possible role of phosphatidylinositol 3-kinase/protein kinase B pathway

2002 ◽  
Vol 174 (2) ◽  
pp. 195-204 ◽  
Author(s):  
SB Meroni ◽  
MF Riera ◽  
EH Pellizzari ◽  
SB Cigorraga
Keyword(s):  
Protein Kinase ◽  
Sertoli Cell ◽  
Mechanism Of Action ◽  
Sertoli Cells ◽  
Cell Function ◽  
Protein Kinase B ◽  
Lactate Production ◽  
Phosphatidylinositol 3 Kinase ◽  
Stimulation Of

The FSH molecular mechanism of action is best recognized for its stimulation of the adenylyl cyclase/cAMP pathway via activation of a G protein. Recently, links between cAMP, phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB) signaling pathways in thyroid and granulosa cells have been observed. The aim of this study was to investigate the possible role of the PI3K/PKB pathway in FSH regulation of Sertoli cell function. Twenty-day-old rat Sertoli cell cultures were used. An increase in phosphorylated PKB (P-PKB) levels in response to FSH and dibutyryl-cAMP was observed. These increments in P-PKB levels were not observed in the presence of two PI3K inhibitors, wortmannin and Ly 294002. Inhibition of protein kinase A (PKA) by H89 did not decrease FSH stimulation of P-PKB levels. Taken together, these results indicate that FSH increases P-PKB levels in a PI3K-dependent and PKA-independent manner in rat Sertoli cells. In addition, wortmannin partially inhibited the ability of FSH to stimulate two well-known parameters of Sertoli cell function - transferrin secretion and lactate production - at doses equal to or lower than 0.1 microM. Related to lactate production, a decrease in FSH stimulation of lactate dehydrogenase activity and of basal and FSH-stimulated glucose uptake was observed in the presence of wortmannin. These metabolic changes were in most cases accompanied by changes in the levels of P-PKB. Altogether, these results suggest a meaningful role of the PI3K/PKB pathway in the mechanism of action of FSH in rat Sertoli cells.

scholarly journals Assessment of the roles of mitogen-activated protein kinase and phosphatidyl inositol 3-kinase/protein kinase B pathways in the basic fibroblast growth factor regulation of Sertoli cell function

2003 ◽  
Vol 31 (2) ◽  
pp. 279-289 ◽  
Author(s):  
MF Riera ◽  
SB Meroni ◽  
EH Pellizzari ◽  
SB Cigorraga
Keyword(s):  
Protein Kinase ◽  
Sertoli Cell ◽  
Kinase Inhibitors ◽  
Cell Function ◽  
Lactate Production ◽  
Phosphatidyl Inositol ◽  
Mitogen Activated Protein Kinase ◽  
Ldh Activity ◽  
Mitogen Activated Protein ◽  
Stimulation Of

Basic fibroblast growth factor (bFGF) belongs to the large set of intratesticular regulators that provide the fine tuning of cellular processes implicated in the maintenance of spermatogenesis. The aim of the present study was to determine the participation of mitogen-activated protein kinase (MAPK) and phosphatidyl inositol 3-kinase/protein kinase B (PI3K/PKB) pathways in bFGF regulation of Sertoli cell function. Twenty-day-old rat Sertoli cell cultures were used. Stimulation of the cultures with bFGF showed a time-dependent increment in phosphorylated MAPK and PKB levels that reached maximal values in 5-min incubations. MAPK kinase inhibitors U0126 (U) and PD98059 (PD) and a PI3K inhibitor wortmannin (W) were able to block the stimulatory effects of bFGF on phosphorylated MAPK and PKB levels respectively. The participation of MAPK- and PI3K/PKB-signaling pathways in the regulation by bFGF of two well-known Sertoli cell-differentiated functions, lactate and transferrin production, was next explored. As for lactate production, PD and W did not modify the ability of bFGF to stimulate lactate production. However, a combination of PD and W partially impaired the increase in lactate production elicited by bFGF. The participation of MAPK- and PI3K/PKB-signaling pathways in the regulation by bFGF of glucose uptake and lactate dehydrogenase (LDH) activity was also analysed. In this respect, it was observed that W markedly decreased basal and bFGF-stimulated glucose uptake and that U and PD did not modify it. On the other hand, U and PD decreased the stimulation of LDH activity by bFGF whereas W did not modify it. As for transferrin production, while both MAPK kinase inhibitors partially decreased the ability of bFGF to stimulate transferrin secretion, the PI3K inhibitor did not modify it. In summary, the results demonstrated that bFGF stimulates MAPK- and PI3K/PKB-dependent pathways in rat Sertoli cells. Moreover, these results showed that while bFGF utilizes the MAPK pathway to regulate transferrin production and LDH activity, it uses the PI3K/PKB pathway to regulate glucose transport into the cell.

Inositol lipid breakdown as a step in α-adrenergic stimulus-response coupling

1985 ◽  
Vol 68 (s10) ◽  
pp. 43s-46s ◽  
Author(s):  
Robert H. Michell
Keyword(s):  
Protein Kinase C ◽  
Cell Function ◽  
Receptor Activation ◽  
Stimulus Response ◽  
Kinase C ◽  
Inositol 1,4,5 Trisphosphate ◽  
Messenger Molecules ◽  
Hydrolysis Of ◽  
Major Mediator ◽  
Stimulation Of

1. A widespread, and maybe universal, response to stimulation of α-adrenoceptors is inositol lipid hydrolysis: the receptor-coupled event is probably hydrolysis of phosphatidylinositol 4,5-bisphosphate. This reaction generates two second messenger molecules. 2. Inositol 1,4,5-trisphosphate may be responsible for the intracellular mobilization of Ca2+ that has long been recognized as a major mediator of the effects of α-receptor activation. In addition, the released 1,2-diacylglycerol probably contributes to control of cell function through activation of protein kinase C.

scholarly journals Assessment of magnetic flux density properties of electromagnetic noninvasive phrenic nerve stimulations for environmental safety in an ICU environment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
K. Friedrich Kuhn ◽  
Julius J. Grunow ◽  
Pascal Leimer ◽  
Marco Lorenz ◽  
David Berger ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Magnetic Flux ◽  
Flux Density ◽  
Muscle Fiber ◽  
Phrenic Nerve ◽  
Magnetic Flux Density ◽  
Training Center ◽  
Electromagnetic Stimulation ◽  
Stimulation Of

AbstractDiaphragm weakness affects up to 60% of ventilated patients leading to muscle atrophy, reduction of muscle fiber force via muscle fiber injuries and prolonged weaning from mechanical ventilation. Electromagnetic stimulation of the phrenic nerve can induce contractions of the diaphragm and potentially prevent and treat loss of muscular function. Recommended safety distance of electromagnetic coils is 1 m. The aim of this study was to investigate the magnetic flux density in a typical intensive care unit (ICU) setting. Simulation of magnetic flux density generated by a butterfly coil was performed in a Berlin ICU training center with testing of potential disturbance and heating of medical equipment. Approximate safety distances to surrounding medical ICU equipment were additionally measured in an ICU training center in Bern. Magnetic flux density declined exponentially with advancing distance from the stimulation coil. Above a coil distance of 300 mm with stimulation of 100% power the signal could not be distinguished from the surrounding magnetic background noise. Electromagnetic stimulation of the phrenic nerve for diaphragm contraction in an intensive care unit setting seems to be safe and feasible from a technical point of view with a distance above 300 mm to ICU equipment from the stimulation coil.

The Appearance Of PF1 And PF3 In Activated Human Platelets

1981 ◽  
Author(s):  
H Sandberg ◽  
A P Bodet ◽  
F A Dombrosei ◽  
L O Andersson ◽  
B R Lentz
Keyword(s):  
Human Platelets ◽  
Dense Granule ◽  
Void Volume ◽  
Factor V ◽  
Dense Granules ◽  
Protein Particles ◽  
Hydrolysis Of ◽  
Platelet Pellet ◽  
Stimulation Of

Collagen and thrombin induced platelet activation were examined, in vitro, with regard to the appearance of surface-associated Factor V-like activity (PF1) and catalytic phospholipid-like surface activity (PF3). Two test systems were used: a clotting assay (a modified KAPTT) and a chromogenic substrate assay (maximum hydrolysis of S-2238). Following stimulation of normal platelets, both PF1 and PF3 appeared simultaneously in the supernatant and platelet pellet. When normal platelets were collected and carefully washed in a buffer containing adenosine, PGE1, and theophylline, the appearance of both PF1 and PF3 was blocked, as was the release of ATP from dense granules, the release of β-TG and PF4 from α-granules, and the occurrence of aggregation. When platelets were collected in this same inhibitor-containing buffer, and then gel filtered/centrifuge-washed in an inhibitor-free buffer, the appearance of PF1 and PF3 was still blocked. This occurred even though release of ATP, β-TG and PF4 as well as aggregation followed a pattern equivalent to platelets never exposed to these inhibitors. When the release supernatant from normal platelets isolated in the absence of inhibitors was gel filtered on Sepharose CL-4B in the presence of EDTA, the carbohydrate-free, lipid- protein particles (70-170nm diam.) that provide PF3 appeared in the void volume. When the release supernatant from normal platelets was gel filtered in the presence of Ca2+, both, PF1 and PF3 eluted in the void volume. With platelets isolated from severe F.V-deficient donors, only PF3 was found in the void volume, in the presence or absence of Ca2+. It seems that the appearance of PF1 and PF3 as coagulant activities is completely separate from both the release of dense granule and α-granule contents as well as platelet aggregation and that the appearance of PF1 requires the presence of Ca2+.

Effects of l-leucine, its 2-keto acid metabolite and its nonmetabolized analogue on rat tumoral islet cell function

1988 ◽  
Vol 1 (1) ◽  
pp. 69-76 ◽  
Author(s):  
V. Leclercq-Meyer ◽  
J. Marchand ◽  
A. Sener ◽  
F. Blachier ◽  
W. J. Malaisse
Keyword(s):  
Insulin Release ◽  
Cell Function ◽  
Islet Cells ◽  
Adenine Nucleotides ◽  
Secretory Response ◽  
Acid Metabolite ◽  
Dual Effect ◽  
Islet Cell Function ◽  
Insulinoma Cells ◽  
Stimulation Of

ABSTRACT l-Leucine and 2-ketoisocaproate stimulated insulin release from perifused rat tumoral islet cells (RINm5F line). The secretory response coincided with an increase in the intracellular ATP/ADP ratio, a stimulation of 45Ca outflow from cells perifused in the presence of extracellular Ca2+, and an increase in 32P efflux from cells prelabelled with radioactive orthophosphate. In contrast to d-glucose, however, l-leucine or 2-ketoisocaproate failed to decrease 86Rb outflow, to inhibit 45Ca outflow from cells perifused in the absence of Ca2+ and to enhance the labelling of inositol-containing phospholipids in cells exposed to myo-[2-3H]inositol. These findings suggest that d-glucose, l-leucine and 2-ketoisocaproate exert dissimilar effects on the subcellular distribution of adenine nucleotides and/or 86Rb. The nonmetabolized analogue of l-leucine, 2-aminobicyclo-[2.2.1]heptane-2-carboxylic acid (BCH), also caused an initial stimulation of insulin release and 32P efflux, but this was soon followed by a severe and irreversible inhibition of insulin output, associated with a permanent enhancement of 86Rb outflow. The dual ionic and secretory response to BCH is interpreted in the light of its dual effect on the catabolism of endogenous amino and fatty acids, and raises the view that BCH could be used to interfere with the function of insulinoma cells.

scholarly journals Purinergic stimulation of rat cardiomyocytes induces tyrosine phosphorylation and membrane association of phospholipase Cγ: a major mechanism for InsP3 generation

1996 ◽  
Vol 318 (2) ◽  
pp. 723-728 ◽  
Author(s):  
Michel PUCEAT ◽  
Guy VASSORT
Keyword(s):  
Tyrosine Kinase ◽  
Time Course ◽  
Kinase Inhibitor ◽  
Extracellular Atp ◽  
Rat Cardiomyocytes ◽  
Major Mechanism ◽  
Adult Rat ◽  
Hydrolysis Of ◽  
Purinergic Stimulation ◽  
Stimulation Of

Phospholipase Cγ (PLCγ) expression and activation by a purinergic agonist were investigated in adult rat cardiomyocytes. PLCγ is expressed in isolated cardiomyocytes. Stimulation of cells with extracellular ATP induces a rapid increase in membrane-associated PLCγ immunoreactivity most probably due to redistribution of the lipase from the cytosol to the membrane. The purine triggers a significant phosphorylation on tyrosine residues of a cytosolic pool of PLCγ with a time course that correlates with that of translocation. Extracellular ATP also increases intracellular Ins(1,4,5)P3 content. All these events (translocation and phosphorylation of PLCγ, InsP3 formation) are blocked by genistein, a tyrosine kinase inhibitor. The purinergic effect on both PLCγ translocation and phosphorylation are Ca-sensitive. We thus propose that the purinergic stimulation activates a non-receptor tyrosine kinase that phosphorylates PLCγ in the presence of an increased Ca level and induces PLCγ redistribution to the membrane. There, PLCγ becomes activated leading to the hydrolysis of phosphatidylinositol diphosphate and in turn Ins(1,4,5)P3 formation. This cascade of events may play a significant role in the induction of arrhythmogenesis by purinergic agonists.

Red cell function at extreme altitude on Mount Everest

1984 ◽  
Vol 56 (1) ◽  
pp. 109-116 ◽  
Author(s):  
R. M. Winslow ◽  
M. Samaja ◽  
J. B. West
Keyword(s):  
Cell Function ◽  
Blood Gases ◽  
Hemoglobin Concentration ◽  
Respiratory Alkalosis ◽  
Blood Collection ◽  
Red Cell ◽  
Arterial Blood ◽  
Extreme Altitude ◽  
2,3 Dpg

As part of the American Medical Research Expedition to Everest in 1981, we measured hemoglobin concentration, red cell 2,3-diphosphoglycerate (2,3-DPG), Po2 at which hemoglobin is 50% saturated (P50), and acid-base status in expedition members at various altitudes. All measurements were made in expedition laboratories and, with the exception of samples from the South Col of Mt. Everest (8,050 m), within 2 h of blood collection. In vivo conditions were estimated from direct measurements of arterial blood gases and pH or inferred from base excess and alveolar PCO2. As expected, increased 2,3-DPG was associated with slightly increased P50, when expressed at pH 7.4. Because of respiratory alkalosis, however, the subjects' in vivo P50 at 6,300 m (27.6 Torr) was slightly less than at sea level (28.1 Torr). The estimated in vivo P50 was progressively lower at 8,050 m (24.9 Torr) and on the summit at 8,848 m (19.4 Torr in one subject). Our data suggest that, at extreme altitude, the blood O2 equilibrium curve shifts progressively leftward because of respiratory alkalosis. This left shift protects arterial O2 saturation at extreme altitude.

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